The process of membrane fusion occurs in various cellular activities such as endocytosis, exocytosis and fertilization. The transport of drugs and other substances into cells may be enhanced by incorporating them in phospholipid vesicles, and fusing the vesicles with the cells. The objectives of this project are: (1) Analysis and prediction of the combined effect of various factors affecting the fusion of pure or mixed phospholipid vesicles. The factors to be considered include composition and size of vesicles, concentration, temperature, ionic strength and specific ions such as Ca2 ion and Mg2 ion. (2) Analysis and prediction of the fusion of phospholipid vesicles with cells, and of the optimal conditions for transferring drugs and other substances to cells by preloading vesicles with these substances and fusing them with target cells. (3) Analysis of the thermodynamics of vesicle population with an emphasis on the question of aggregation of vesicles and micelles, optimal vesicle size, and effect of various ions. The study will concentrate on interdisciplinary theoretical analysis, but small scale experimental tests of the theory will also be performed, including optical density, light scattering, electron microscopy, electrophoretic mobility, and scanning calorimetry measurements. The kinetics of aggregation of vesicles will be studied by taking into account cation binding. The kinetics of vesicle-vesicle fusion will be studied by employing a newly developed program based on mass action model. The calculations will be compared with experiments measuring a fluorescent reaction produced only in the interior of fused vesicles. The calculated distribution of fused vesicles will be tested by light scattering.